Vincent J. Gnanapragasam
A5025926870- Prostate Cancer Treatment and Research
- Prostate Cancer Diagnosis and Treatment
- Cancer Genomics and Diagnostics
- Bladder and Urothelial Cancer Treatments
- MRI in cancer diagnosis
- Global Cancer Incidence and Screening
- Urologic and reproductive health conditions
- Radiomics and Machine Learning in Medical Imaging
- Molecular Biology Techniques and Applications
- Epigenetics and DNA Methylation
- Cancer, Lipids, and Metabolism
- Renal cell carcinoma treatment
- Genetic factors in colorectal cancer
- Statistical Methods in Clinical Trials
- Urological Disorders and Treatments
- Health Systems, Economic Evaluations, Quality of Life
- Colorectal Cancer Screening and Detection
- Cancer-related molecular mechanisms research
- Fibroblast Growth Factor Research
- RNA modifications and cancer
- Genital Health and Disease
- Medical Imaging Techniques and Applications
- Single-cell and spatial transcriptomics
- Genomics and Chromatin Dynamics
- DNA Repair Mechanisms
University of Cambridge
2016-2025
Cambridge University Hospitals NHS Foundation Trust
2016-2025
Prostate Cancer UK
2021-2025
Addenbrooke's Hospital
2015-2024
Prostate Cancer Research
2001-2023
National Health Service
2023
MRC Clinical Trials Unit at UCL
2023
Bridge University
2020-2023
Royal Marsden NHS Foundation Trust
2021
Institute of Cancer Research
2021
Between 1999 and 2009 in the United Kingdom, 82,429 men between 50 69 years of age received a prostate-specific antigen (PSA) test. Localized prostate cancer was diagnosed 2664 men. Of these men, 1643 were enrolled trial to evaluate effectiveness treatments, with 545 randomly assigned receive active monitoring, 553 undergo prostatectomy, radiotherapy.
Abstract Tumour heterogeneity in primary prostate cancer is a well-established phenomenon. However, how the subclonal diversity of tumours changes during metastasis and progression to lethality poorly understood. Here we reveal precise direction metastatic spread across four lethal patients using whole-genome ultra-deep targeted sequencing longitudinally collected tumours. We find one case surgical bed causing local recurrence, another cross-metastatic site seeding combining with dynamic...
BackgroundUnderstanding the heterogeneous genotypes and phenotypes of prostate cancer is fundamental to improving way we treat this disease. As yet, there are no validated descriptions subgroups derived from integrated genomics linked with clinical outcome.MethodsIn a study 482 tumour, benign germline samples 259 men primary cancer, used integrative analysis copy number alterations (CNA) array transcriptomics identify genomic loci that affect expression levels mRNA in an quantitative trait...
Genetic profiles of the bladder Depending on environment individual, human can be exposed to carcinogens as they are flushed through body. Lawson et al. and Li examined genetic composition laser-dissected microbiopsies from normal cancer cells collected urothelium, a specialized epithelium lining lower urinary tract (see Perspective by Rozen). These complementary studies identified mutational landscape urothelium various sequencing strategies high heterogeneity within between individuals...
Abstract Ionizing radiation is a potent carcinogen, inducing cancer through DNA damage. The signatures of mutations arising in human tissues following vivo exposure to ionizing have not been documented. Here, we searched for 12 radiation-associated second malignancies different tumour types. Two somatic mutation characterize irrespective type. Compared with 319 radiation-naive tumours, tumours carry median extra 201 deletions genome-wide, sized 1–100 base pairs often microhomology at the...
Tumor behavior is intricately dependent on the oncogenic properties of cancer cells and their multi-cellular interactions. To understand these dependencies within wider microenvironment, we studied over 270,000 single-cell transcriptomes 100 microdissected whole exomes from 12 patients with kidney tumors, prior to validation using spatial transcriptomics. Tissues were sampled multiple regions tumor core, tumor-normal interface, normal surrounding tissues, peripheral blood. We find that...
BackgroundLong-term patient-reported outcomes are needed to inform treatment decisions for localized prostate cancer.MethodsPatient-reported of 1643 randomly assigned participants in the ProtecT (Prostate Testing Cancer and Treatment) trial were evaluated assess functional quality-of-life impacts prostatectomy, radiotherapy with neoadjuvant androgen deprivation, active monitoring. This article focuses on from 7 12 years using mixed effects linear logistic models.ResultsResponse rates...
To determine the accuracy of multiparametric magnetic resonance imaging (mpMRI) during learning curve radiologists using MRI targeted, transrectal ultrasonography (TRUS) guided transperineal fusion biopsy (MTTP) for validation.Prospective data on 340 men who underwent mpMRI (T2-weighted and diffusion-weighted MRI) followed by MTTP prostate biopsy, was collected according to Ginsburg Study Group Standards Reporting Diagnostic Accuracy standards. were reported two experienced scored a Likert...
Objectives To define terms and processes agree on a minimum dataset in relation to transperineal prostate biopsy procedures enhanced diagnostics. identify the need for further evaluation establish collaborative research practice. Patients Methods A 19‐member multidisciplinary panel rated 66 items their appropriateness definition be incorporated into international databank using R esearch D evelopment/ U niversity of C alifornia L os ngeles ppropriateness M ethod. The item list was developed...
The ProtecT trial reported intention-to-treat analysis of men with localised prostate cancer (PCa) randomly allocated to active monitoring (AM), radical prostatectomy, and external beam radiotherapy. To determine report outcomes according treatment received in randomised choice cohorts. This study focuses on secondary care. Men clinically at one nine UK centres were invited participate the comparing AM, Two cohorts included 1643 who agreed be randomised; 997 declined randomisation chose...
Estrogen Receptor-β (ERβ) has been implicated in many cancers. In prostate and breast cancer its function is controversial, but genetic studies implicate a role progression. Much of the confusion around ERβ stems from antibodies that are inadequately validated, yet have become standard tools for deciphering role. Using an ERβ-inducible cell system we assessed commonly utilized show one most used antibodies, NCL-ER-BETA, non-specific ERβ. Other limited specificity or only specific...
Abstract Muscle Invasive Bladder Cancer (MIBC) has a poor prognosis. Whilst patients can achieve 6% improvement in overall survival with Neo-Adjuvant Chemotherapy (NAC), many do not respond. Body fluid mutant DNA (mutDNA) may allow non-invasive identification of treatment failure. We collected 248 liquid biopsy samples including plasma, cell pellet (UCP) and supernatant (USN) from spun urine, 17 undergoing NAC. assessed single nucleotide variants copy number alterations mutDNA using...
BackgroundAccurate prognostication is crucial in treatment decisions made for men diagnosed with non-metastatic prostate cancer. Current models rely on prespecified variables, which limits their performance. We aimed to investigate a novel machine learning approach develop an improved prognostic model predicting 10-year cancer-specific mortality and compare its performance existing validated models.MethodsWe derived tested learning-based using Survival Quilts, algorithm that automatically...
The prostate gland produces prostatic fluid, high in zinc and citrate essential for the maintenance of spermatozoa. Prostate cancer is a common condition with limited treatment efficacy castration-resistant metastatic disease, including immune checkpoint inhibitors. Using single-cell RNA-sequencing to perform an unbiased assessment cellular landscape human prostate, we identify subset tumor-enriched androgen receptor-negative luminal epithelial cells increased expression cancer-associated...
To investigate the functional and quality of life (QoL) outcomes treatments for localised prostate cancer inform treatment decision-making.Men aged 50-69 years diagnosed with by prostate-specific antigen testing biopsies at nine UK centres in Prostate Testing Cancer Treatment (ProtecT) trial were randomised to, or chose one of, three treatments. Of 2565 participants, 1135 men received active monitoring (AM), 750 a radical prostatectomy (RP), 603 external-beam radiotherapy (EBRT) concurrent...
Abstract Hyperpolarised magnetic resonance imaging (HP 13 C-MRI) is an emerging clinical technique to detect [1- C]lactate production in prostate cancer (PCa) following intravenous injection of hyperpolarised C]pyruvate. Here we differentiate clinically significant PCa from indolent disease a low/intermediate-risk population by correlating labelling on MRI with the percentage Gleason pattern 4 (%GP4) disease. Using immunohistochemistry and spatial transcriptomics, show that HP C-MRI...
Serial MRI is an essential assessment tool in prostate cancer (PCa) patients enrolled on active surveillance (AS). However, it has only moderate sensitivity for predicting histopathological tumour progression at follow-up, which part due to the subjective nature of its clinical reporting and variation among centres readers. In this study, we used a long short-term memory (LSTM) recurrent neural network (RNN) develop time series radiomics (TSR) predictive model that analysed longitudinal...
RAC 3, one of the p160 family co-activators is known to enhance transcriptional activity a number steroid receptors. As are also androgen receptor (AR) activity, we investigated role 3 in context prostate cancer. In cancer cell lines, found variable levels protein with highest expression seen AR-positive LNCaP cells, moderate AR-negative PC cells and low-level DU 145 cells. Immuno-precipitation studies showed that endogenous interacted AR vivo transfection assays confirmed enhanced activity....
Abstract Androgen deprivation therapy (ADT) is a key primary treatment for advanced and metastatic prostate cancer an important neoadjuvant before radiotherapy. We evaluated 3.0 T dynamic contrast‐enhanced MRI diffusion‐weighted (DW) in monitoring ADT response. Twenty‐three consecutive patients with treated by were included. Imaging was performed at baseline 3 months posttreatment ADT. After there significant reduction all parameters measured tumor regions of interest ( K trans , k ep v p...